Patent GB-669046-A (GB)
Title: Improvements in or relating to antiseptic compounds and methods of preparing the same
Filed: 1948-10-22
Abstract: Acridane salts of the formula <FORM:0669046/IV (b)/1> or tautomeric forms thereof, where R is alkyl or cycloalkyl with 1-14 carbon atoms, X is hydrogen or one or more halogen, alkyl or alkoxy groups, Y is a hydrocarbon radical of 1-10 carbon atoms and Z is a mineral acid anion, are obtained by treating the corresponding 9-alkoxyphenyl-X : Y-substituted acridols with a mineral acid (including a gaseous hydrogen halide).  The acridol is made by reacting the lithium derivative of an alkoxy-benzene with an X : Y-substituted acridone and treating the product with gaseous hydrogen halide to give an acid addition salt of a compound of the above formula; hydrogen halide is lost on drying with heat or adding a neutralizing agent such as calcium carbonate, and addition of alkali then gives the acridol (9-alkoxyphenyl-9-hydroxy - X : Y - substituted acridane).  For purification, the acridol may be warmed with methanol or other alkanol to give the crystalline 9-alkoxy-compound which generates the salt of the above formula on treatment with a mineral acid. Examples show the preparation of acridols and acridane salts where OR is p-methoxy, p-n-hexoxy, o-methoxy, p-n-butoxy, p-n-octyloxy, p-2-ethylbutoxy, p-n-decyloxy, p-cyclohexyloxy, m-methoxy and p-n-tetradecyloxy, Y is methyl, phenyl, ethyl, n-decyl and benzyl, and X is hydrogen, 2-methoxy or 1-chloro-4-methyl.  The anion Z may be chloride, bromide, iodide or bisulphate.  N-Alkyl-acridones are made by ring-closing phenyl-anthranilic acid with sulphuric acid or with phosphorus pentachloride and aluminium chloride and alkylating with dialkyl sulphate.  Alternatively the alkali metal derivative of acridone is made and treated with an alkyl halide. N-Aralkyl-acridones are made similarly. N-Aryl-acridones are made by ring-closing triphenylamine carboxylic acids.  Specified products are N-methyl, N-hexyl and N-benzyl-acridones.  Lithium derivatives of alkoxy-benzenes are obtained by reacting lithium metal with alkoxyphenyl halides in ether, e.g. p-hexoxyphenyl iodide, p-hexoxyphenyl bromide, o- and p-bromoanisole and p-butoxyphenyl bromide.  Other products are mentioned.  In the Specification as open to inspection under Sect. 91 it is stated that the aromatic nuclei may carry other substituents and that one of these rings may be saturated or heterocyclic. Further examples are given of the production of acridols and the corresponding 9-alkoxy compounds, viz. 9-(p-hexoxyphenyl)-10 - methyl - 9 - acridol, 9 - (p - methoxyphenyl) - 10 - phenyl - 9 - acridol, 9 - (o - methoxyphenyl) - 10 - methyl - 9 - acridol, 9 - (p - butoxyphenyl) - 10 - methyl - 9 - acridol, 9 - (p - hexoxyphenyl) - 10 - ethyl - 9 - acridol, 9 - (p - hexoxyphenyl) - 10 - benzyl - 9 - acridol, 9 - (p - octyloxyphenyl) - 10-methyl-9-acridol, 9-(p-2-ethylhexoxyphenyl) - 10 - methyl - 9 - acridol, 2-methoxy-9-(p-hexoxyphenyl)-10-methyl-9-acridol, 1 - chloro - 9 - (p - hexoxyphenyl) - 4 : 10 - dimethyl - 9 - acridol and 9 - (p - decyloxyphenyl) - 10 - methyl - 9 - acridol, and the methyl, ethyl and butyl ethers of the above. Other compounds mentioned are 9-(p-hexoxyphenyl) - 10 - decyl - 9 - acridol and 9 - (p - tetradecyloxyphenyl) - 10 - methyl - 9 - acridol and their methyl ethers.  The N-methylation of 2-methoxyacridone and 1-chloro-4-methylacridone is also mentioned, using dimethyl sulphate. This subject-matter does not appear in the Specification as accepted.